Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes
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2015
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Nature Research
Resumen
Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted
cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo
dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to
redifferentiate chondrocytes isolated from osteoarthritis (OA) patients. We used morphological,
histological and immunological analysis together with a RT-PCR detection of collagen I and
collagen II gene expression to show that chondrocytes isolated from articular cartilage biopsies of
patients and subjected to long-term culture undergo dedifferentiation and that these cells can be
redifferentiated following treatment with the chimeric Activin A/BMP2 ligand AB235. Examination
of AB235-treated cell pellets in both in vitro and in vivo experiments revealed that redifferentiated
chondrocytes synthesized a cartilage-specific extracellular matrix (ECM), primarily consisting of
vertically-orientated collagen fibres and cartilage-specific proteoglycans. AB235-treated cell pellets
also integrated into the surrounding subcutaneous tissue following transplantation in mice as
demonstrated by their dramatic increase in size while non-treated control pellets disintegrated
upon transplantation. Thus, our findings describe an effective protocol for the promotion of
redifferentiation of autologous chondrocytes obtained from OA patients and the formation of a
cartilage-like ECM that can integrate into the surrounding tissue in vivo.
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Jiménez G*, López-Ruiz E*, Kwiatkowski W, Montañez E, Arrebola F, Carrillo E, Gray PC, Izpisua Belmonte JC, Choe S, Perán M, Marchal JA. Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes. Sci Rep. 2015 Nov 13;5:16400. doi: 10.1038/srep16400.